Abstract
Des-acyl ghrelin, although devoid of binding to ghrelin receptor (GRLN), exerts many biological effects, including regulation of glucose and lipid metabolism. Indeed, des-acyl ghrelin promotes pancreatic β-cell and human islet cell survival and prevents diabetes in streptozotocin (STZ) treated rats. We investigated whether des-acyl ghrelin fragments excluding serine(3), which is essential for binding to GRLN, would display similar actions. Among the different compounds tested, des-acyl ghrelin((6-13)) and des-acyl ghrelin((6-13)) with alanine substitutions or cyclization, but not with d-amino acid substitutions, showed the best survival effect, similar to des-acyl ghrelin. Des-acyl ghrelin((6-13)) even prevented diabetes in STZ-treated rats and protected human circulating angiogenic cells from oxidative stress and senescence, similar to des-acyl ghrelin. These results suggest that not only full-length des-acyl ghrelin but also short des-acyl ghrelin fragments have clear beneficial effects on several tissues in vitro and in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Cell Survival / drug effects
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Cellular Senescence / drug effects
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / pathology
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Diabetes Mellitus, Experimental / prevention & control*
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Endothelial Cells / cytology
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Endothelial Cells / drug effects
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Ghrelin / analogs & derivatives*
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Ghrelin / chemistry*
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Ghrelin / pharmacology
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Humans
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Insulin-Secreting Cells / cytology
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Insulin-Secreting Cells / drug effects*
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Islets of Langerhans / cytology
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Islets of Langerhans / drug effects*
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Models, Molecular
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Molecular Sequence Data
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Oxidative Stress
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Peptide Fragments / chemistry*
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Peptide Fragments / pharmacology
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology
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Peptidomimetics / chemistry*
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Peptidomimetics / pharmacology
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Rats
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Rats, Sprague-Dawley
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Stem Cells / metabolism
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Stem Cells / pathology
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Stereoisomerism
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Streptozocin
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Structure-Activity Relationship
Substances
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Ghrelin
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Peptide Fragments
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Peptides, Cyclic
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Peptidomimetics
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Streptozocin